The desynaptic (dy) and desynaptic1 (dsy1) mutations in maize (Zea mays L) cause distinct telomere-misplacement phenotypes during meiotic prophase

During meiotic prophase, telomeres actively attach themselves to the nuclear envelope and cluster in an arrangement called the bouquet. The bouquet is unique to meiosis, highly conserved, and thought to facilitate homologous chromosome synapsis. Analy sis of three-dimensional fluorescence in situ hybridization (3-D FISH) image data has been employed to characterize the bouquet in fixed pollen mother cells of maize (Zea mays L.). In order to examine the function of the bouquet further, several meiotic mutants were screened for telomeric defects using 3-D FISH as an assay. Two mutants, desynaptic (dy) and desynaptic1 (dsy1), were found to exhibit novel telomere-misplacement phenotypes. In both cases, the telomere-associated mutant phenotypes occurred prior to what was previously reported as the earliest affected stage. Three alleles of the desynaptic1 mutation (dsy1-1, dsy1-9101, and dsy1-9307) resulted in a partial bouquet phenotype at the zygotene stage of meiotic prophase. By contrast, dy nuclei contained apparently normal bouquets, but then resulted in a premature intranuclear localization of telomeres at the pachytene stage, when telomeres normally disperse but remain attached to the nuclear envelope. The dsy1 mutation is known to impair the fidelity and progression of homologous synapsis, whereas the dy mutation is known to reduce recombination rates. If the telomere misplacements are primary defects of these mutants, then these data would be consistent with the hypothesis that meiotic telomeres have at least two separable functions, one involving proper homologous chromosome synapsis at the bouquet stage and another involving post-bouquet cross-over control.     

Improper chromosome synapsis is associated with elongated RAD51 structures in the maize<Emphasis Type="Italic"> desynaptic2</Emphasis> mutant

The RecA homolog, RAD51, performs a central role in catalyzing the DNA strand exchange event of meiotic recombination. During meiosis, RAD51 complexes develop on pairing chromosomes and then most disappear upon synapsis. In the maize meiotic mutant desynaptic2 (dsy2), homologous chromosome pairing and recombination are reduced by ~70% in male meiosis. Fluorescent in situ hybridization studies demonstrate that a normal telomere bouquet develops but the pairing of a representative gene locus is still only 25%. Chromosome synapsis is aberrant as exemplified by unsynapsed regions of the chromosomes. In the mutant, we observed unusual RAD51 structures during chromosome pairing. Instead of spherical single and double RAD51 structures, we saw long thin filaments that extended along or around a single chromosome or stretched between two widely separated chromosomes. Mapping with simple sequence repeat (SSR) markers places the dsy2 gene to near the centromere on chromosome 5, therefore it is not an allele of rad51. Thus, the normal dsy2 gene product is required for both homologous chromosome synapsis and proper RAD51 filament behavior when chromosomes pair. Edited by: P. Moens     

Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage

Bovine brucellosis is a serious zoonotic disease affecting some populations of Rocky Mountain elk (Cervus elaphus nelsoni) and bison (Bison bison) in the Greater Yellowstone Area, USA. The fear that elk and/or bison may spread Brucella abortus to livestock has prompted efforts to reduce or eliminate the disease in wildlife. Brucella abortus strain RB51 (RB51) vaccine has recently been approved for use in cattle. Unlike strain 19 vaccine, RB51 does not cause false positive reactions on standard brucellosis serologic tests. If effective, it may become the vaccine of choice for wildlife. In February 1995, 45 serologically negative female elk calves were trapped and taken to the Sybille Wildlife Research and Conservation Education Unit near Wheatland, Wyoming, USA. In May 1995, 16 of these elk calves were hand-vaccinated with 1 x 10(9) colony forming units (CFU) of RB51, 16 were vaccinated with 1 x 10(8) CFU RB51 by biobullet, and 13 were given a saline placebo. The elk were bred in fall of 1996 and they were challenged with 1 x 10(7) CFU of B. abortus strain 2308 by intraconjunctival inoculation in March 1997. Thirteen (100%) control elk aborted, 14 (88%) hand-vaccinated elk aborted, and 12 (75%) biobullet vaccinated elk aborted or produced nonviable calves. These results suggest that a single dose of 1 x 10(8) to 1 x 10(9) CFU RB51 does not provide significant protection against B. abortus induced abortion in elk. However, the vaccine appears to be safe at this dose and additional study may reveal a more effective RB51 vaccine regimen for elk.     

Structure-activity relationship studies on 2-heteroaryl-4-arylimidazoles NPY5 receptor antagonists

A series of 2-heteroaryl-4-arylimidazoles with potent in vitro activity at the NPY5 receptor was developed. Introduction of electron-withdrawing groups on the 4-aryl ring led to a significant improvement of in vitro potency. Several analogues from this series had anorectic activity in rodent feeding models, but were also found to have undesired behavioral effects in spontaneous locomotor activity.     

Effect of flutamide on survival in patients with pancreatic cancer: results of a prospective,randomised, double blind,placebo controlled trial

Objectives: To assess whether flutamide (Drogenil), a pure androgen receptor blocking agent, improves survival in patients with pancreatic carcinoma and thus whether testosterone is a major growth factor for this tumour. Design: A prospective, randomised, double blind placebo controlled trial. Subjects: 49 patients with a clinical diagnosis of pancreatic carcinoma. Interventions: 24 patients received flutamide and 25 received placebo. Main outcome measures: Death of the patient. Results: Analysis of all patients at 6 months and 1 year showed 14 and eight patients alive, respectively, in the flutamide group compared with 10 and one in the placebo group. After exclusion of those patients in both groups who received less than 6 weeks’ treatment because of advanced disease and early death the comparable results were 14 (88%) and eight (50%) alive in the flutamide group compared with 10 (50%) and one (5%) in the placebo group. Median survival for all patients was 8 months in the flutamide group compared with 4 months in the placebo group. With the 6 week exclusions median survival was 12 months compared with 5 months, respectively. Conclusions: This study supports the concept that testosterone is a growth factor for pancreatic carcinoma and that blockade of androgen receptors offers an appropriate new approach to treatment.

Key messages

• Previous work suggests that androgens may be involved in the growth of pancreatic cancer
• This study shows that the antiandrogen flutamide doubles median survival in patients with pancreatic cancer
• The treatment is well tolerated by patients with minimal side effects, an important consideration in those with advanced malignant disease
• The concept that testosterone may be a growth factor in pancreatic adenocarcinoma is supported by this trial

     

The effect of membrane-bound beta-lactamase on linoleic acid sensitivity in Staphylococcus aureus

The presence of a plasmid conferring resistance to penicillin (PC plasmid, e.g. pI258blaI-) in Staphylococcus aureus NCTC 8325 increases the sensitivity of such a bacterium to the growth inhibitory effects of linoleic acid, whereas a plasmid conferring resistance to tetracycline does not affect linoleic acid sensitivity. The increased linoleic acid sensitivity of bacteria containing a PC plasmid may be related to the penicillinase protein itself since (i) strains having inducible penicillinase show increased sensitivity only after induction, (ii) strains in which penicillinase is directed from chromosomal or plasmid-borne genes show similar increased linoleic acid sensitivity and (iii) notwithstanding the above, the linoleic acid inhibitory effect is enhanced in a strain in which penicillinase activity is greatly reduced by a point mutation in the structural gene for penicillinase. The enhanced linoleic acid sensitivity seems to require the membrane-bound penicillinase since added extracellular penicillinase does not confer this sensitivity, and there appears to be a specific interaction between the membrane-bound penicillinase activity and linoleic acid.     

Variation in ovule and seed size and associated size-number trade-offs in angiosperms

Unlike pollen and seed size, the extent and causes of variation in ovule size remain unexplored. Based on 45 angiosperm species, we assessed whether intra- and interspecific variation in ovule size is consistent with cost minimization during ovule production or allows maternal plants to dominate conflict with their seeds concerning resource investment. Despite considerable intraspecific variation in ovule volume (mean CV = 0.356), ovule production by few species was subject to a size-number trade-off. Among the sampled species, ovule volume varied two orders of magnitude, whereas seed volume varied four orders of magnitude. Ovule volume varied positively among species with flower mass and negatively with ovule number. Tenuinucellate ovules were generally larger that crassinucellate ovules, and species with apical placentation (which mostly have uniovulate ovaries) had smaller ovules than those with other placentation types. Seed volume varied positively among species with fruit mass and seed development time, but negatively with seed number. Seeds grew a median 93-fold larger than the ovules from which they originated. Our results provide equivocal evidence that selection minimizes ovule size to allow efficient resource allocation after fertilization, but stronger evidence that ovule size affords maternal plants an advantage in parent-offspring conflict.     

Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity

There is a perception that phentermine pharmacotherapy for obesity increases blood pressure and heart rate (HR), exposing treated patients to increased cardiovascular risk. We collected data from phentermine‐treated (PT) and phentermine‐untreated (P0) patients at a private weight management practice, to examine blood pressure, HR, and weight changes. Records of 300 sequential returning patients were selected who had been treated with a low‐carbohydrate ketogenic diet if their records included complete weight, blood pressure, and HR data from seven office examinations during the first 12 weeks of therapy. The mean time in therapy, time range, and mode was 92 (97.0), 12–624, and 52 weeks. 14% were normotensive, 52% were prehypertensive, and 34% were hypertensive at their first visit or had a previous diagnosis of hypertension. PT subjects systolic blood pressure/diastolic blood pressure (SBP/DBP) declined from baseline at all data points (SBP/DBP ?6.9/?5.0 mm Hg at 26, and ?7.3/?5.4 at 52 weeks). P0 subjects' declines of SBP/DBP at both 26 and 52 weeks were ?8.9/?6.3 but the difference from the treated cohort was not significant. HR changes in treated/untreated subjects at weeks 26 (?0.9/?3.5) and 52 (+1.2/?3.6) were not significant. Weight loss was significantly greater in the PT cohort for week 1 through 104 (P = 0.0144). These data suggest phentermine treatment for obesity does not result in increased SBP, DBP, or HR, and that weight loss assisted with phentermine treatment is associated with favorable shifts in categorical blood pressure and retardation of progression to hypertension in obese patients.